Thank you for recommending us five of the best books on immunology. journalist ed yong started an article last year with this joke:
An immunologist and a cardiologist are kidnapped. the kidnappers threaten to shoot one of them, but promise to spare whoever has made the greatest contribution to humanity. the cardiologist says, “well, I’ve identified drugs that have saved the lives of millions of people.” impressed, the kidnappers turn to the immunologist. “what have you done?” they ask. the immunologist says, “it’s just that the immune system is very complicated…” and the cardiologist says, “just shoot me now.”
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The point, of course, is that the immune system is fearfully complex. but at the beginning of his new book, how to make a vaccine, he offers a more appealing picture, comparing it to Chinese martial arts, which are “elegant, intricate, precise, beautiful in their complexity, surprising in their depth, and so much about restraint, inhibition and tolerance as if it were about taking down an enemy.” Can those of us who are not specialists begin to understand the immune system through books like these?
I’m glad you liked my analogy! The immune system has evolved over a couple billion years, so several layers of complexity have been added as animals got more complex, but the layers work beautifully together. Imagine the arrival of a virus. the ancient ‘innate’ immune system of the patrolling cells acts first to stop it and chemically judge how dangerous it is. these cells then sound the alarm and signal the invader to the advanced immune system that can recognize and remember any intruder, creating an army of cells and antibodies to eliminate it. the next time the same virus tries to invade, the army will be there, ready to repel it. Vaccines work by mimicking a dangerous infection, tricking the immune system into mounting a full immune attack against a harmless attack. this means that when the real virus arrives, the immune army is ready and waiting to prevent infection.
But the immune system must also discriminate between the myriad essential microorganisms in the gut and on the skin and mucous membranes that are essential to health, and those that are dangerous invaders. it must also refrain from attacking normal healthy tissue, despite the many changes they go through during development, pregnancy, aging, and injury (without infection). this is why restriction, inhibition, and tolerance are critical to immune function. Many complex mechanisms work together to prevent immune attack on normal body tissues, but unfortunately these sometimes fail, resulting in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and type I diabetes.
Tell us about your first immunology book recommendation, an investigation into the causes and effects of smallpox vaccines by Edward Jenner.
I’ve always liked to read original sources, or at least immerse myself in them. their warmth and accessibility often surprises. try reading the first page of darwin’s origin of species, for example: ‘my work is now almost done; but as my health is far from good, I have been urged to publish this summary.” Jenner’s book on cowpox vaccination to prevent smallpox, which he himself published in 1798, is no less attractive. the wolf, unarmed of his ferocity, is now lying on the lady’s lap. the cat, the little tiger on our island whose natural home is the forest, is similarly tamed and petted.’ the point he is making relates to how easily animal viruses pass to humans, especially cowpox, of course. Jenner’s book was revolutionary and caused a stir among his readers, especially among members of the establishment. The same, of course, was true of Darwin’s great work some sixty years later. Jenner’s decision to self-publish was brave, but he did not trust that Royal Society scholars would agree to publish his controversial findings.
The book is organized around 23 case histories that together support his historical view of the protective power of cowpox against the most feared disease in human history, smallpox. His study also shows that the protective vaccine can be transferred from one child’s arm to another in an extended series of shots. Much of the writing is concerned with Jenner’s mistaken belief in an infection of horses as the origin of cowpox. but the important message is still loud and clear. Like many great stories, the essential cast of characters is small: Sarah Nelmes, the milkmaid who scratched her hand on a thorn and let in cowpox; james phipps, the gardener’s boy; hannah excell, eleven years old; Mary Pead, five years old; Mary James, six years old; Robert Jenner, eleven months old; and the other members of the little gang of jenner kids immunized against smallpox.
In How to Make a Vaccine, note that the first well-documented attempt at deliberate immunization to prevent smallpox, and indeed any infectious disease, took place in 1721, long before Jenner’s time. however, smallpox remained a global scourge, killing 500 million people in the 20th century before it was finally eradicated. What can we learn from this terrible story?
this question provides a timely take stock of our enthusiastic response to covid-19 vaccines. Edward Jenner’s vaccine was highly effective, but it still took more than a century and a half to kill smallpox. spreading vaccination around the world is often portrayed as a glorious venture of vaccination trips and dedicated pioneers paying arm-in-arm vaccination chains, launching a worldwide vaccination network. But to defeat smallpox, this global network had to become much more like a blanket. The problems facing the smallpox eradication campaign were as diverse as the geography of the earth and the abundant humanity of its nations. in 1958 the world health assembly passed a resolution to eradicate smallpox and this resolution was intensified in 1966.
In the first half of the 20th century, Europe and North America experienced intermittent outbreaks of smallpox, first due to endemic disease and later due to imported cases, especially as World War II drew to a close. The last epidemic in the United States occurred in 1949 in Elsa, Texas, and saw nine infections and one death. intensive vaccination quickly brought the outbreak to an end. By the mid-20th century, Europe and North America were free of smallpox. South America followed in 1971 and global eradication efforts focused on Asia and Africa.
The vaccine was still essentially Jennerian: calf (or sheep or water buffalo) lymph drawn from pustules in the animals’ skin, with stabilizers added. but the campaign in tropical regions now used freeze-dried vaccine, a big step forward. another decisive factor in success was a simple bifurcated applicator and later an automatic “jet” injector that delivered the vaccine using high-pressure air. no needles were required for thousands of inoculations. but the final weapon essential to success was the ingenious use of ring vaccination or containment rather than mass vaccination. This focused strategy was due in large part to the vision of William Foege, noted American vaccinator. ali maow maalin from somalia suffered his last natural case of smallpox in 1977 and became a tireless polio vaccinator. he was in the midst of this campaign when he contracted malaria and died in 2013.
The second of our immunology books is Paul de Kruif’s Microbe Hunters. de kruif appears to have been a colorful character. He fought in the Pancho Villa Expedition, an American intervention in the Mexican Revolution, and later was an adviser to novelist Sinclair Lewis. What is the enduring merit of this book, published in 1926, and how does it help the reader understand the immune system?
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yes, paul de kruif was larger than life in many ways, and this is expressed in his writing. His fruitful relationship with Sinclair Lewis was a springboard for his later success. When Microbe Hunters first appeared in 1926, the Journal of the American Medical Association reviewed it favorably but with some criticism. ‘unfortunately, no doubt to present the material in a vivid and dramatic way, the style has taken on an exaggerated quality, which is annoying. diabolical, infernal, and infernal are the adjectives used most often…these give the book the quality of a best-seller in fiction.” This review proved dramatically prescient: microbe hunters has never been out of print and is perhaps the bestselling medical science book. ever written. among his admirers was young albert sabin, on his way to becoming a dentist until microbe hunters changed his life. sabin went on to produce a polio vaccine that is now very close to ridding the world of polio.
The book begins with Antonie van Leeuwenhoek, the pioneering microscopist who first described microorganisms, and the best way to get a taste of de Kruif’s writing is to taste it. here, van leeuwenhoek’s daughter watches as she makes her big discovery: ‘what could that dear silly father be up to? he narrows his eyes through the lens of it. She mutters guttural words under her breath…and suddenly, Leeuwenhoek’s excited voice! “come here! hurry up! there are little animals in this rainwater…they swim! they play! they are a thousand times smaller than any creature we can see with the naked eye…look! look what I discovered!”
Similarly, the work of thirteen other giants in the field of microbiology is developed, as envisioned by de kruif. The scientific facts are correct (de Kruif was a successful scientist), but the lives and passions of the great pioneers are dramatized in this book, magnified in the narrative. The foundations of what would become the science of immunology are revealed in his accounts of Louis Pasteur, Lazzaro Spallanzani, and Robert Koch. The book then focuses on discoverers of crucial mechanisms in the immune system and disease transmission, as well as early treatments and cures. At that time, in the early 20th century, hygiene theory was widely accepted and germ theory was well established, thus the modern biomedical environment becomes more recognizable. The discovery of antibodies is told through the eyes of Emil von Behring balanced by the story of Élie Metchnikoff, the father of cellular immunology. The last microbe hunter brought to life by de Kruif is Paul Ehrlich, whose “magic bullet” against syphilis was the first example of successful chemotherapy. at least one hero objected to the portrayal of him. Ronald Ross, who discovered the transmission of malaria by mosquitoes, called the book libelous and strongly objected to its depiction of his relationship with Battista Grassi, his rival. but that didn’t stop de kruif’s book from going down in history.
tell us about the beautiful cure: tapping into your body’s natural defenses by daniel m. David
Immunology is notoriously difficult for non-specialists to understand, as the joke you mentioned at the beginning of this interview reminds us. Fortunately, despite being in the midst of a brilliant career in immunology, Daniel Davis has found the time to introduce us to this world with this book. the text unfolds like a thriller, admitting us into the minds of the protagonists as they strive to push the boundaries of understanding. the author allows the tension to build, withholding the answers, so that we share the bewilderment, uncertainty and suppressed emotion of the search until the moment of discovery. it was exciting for me; And I already knew the answers!
the beautiful cure explains the importance of the relationship between the ancient innate immune system and the adaptive immune system that evolved later, conferring the power of immune memory, the basis of all successful vaccination. although in the end it all makes sense and comes together into a beautiful whole, the truth was far from obvious until the late 20th century, and we shared the uncertainties, the frustrations, and the battles to succeed. bitter rivalries and resentments between eminent players are part of his compelling image. There are no guarantees of glory: certain key figures in the history of immunology die without seeing their discoveries triumph. In a tragic moment, a dedicated scientist dies just days before his work is to be recognized with a Nobel Prize.
“the author allows the tension to build, so that we share the bewilderment, uncertainty and suppressed emotion of the search until the moment of discovery”
Davis describes major discoveries in the therapeutic power of personalized antibodies that are transforming new drug development in the 21st century. he explores the biochemical connections between the mind and the body’s response to disease. and then takes us through the fascinating field of restriction, inhibition, and tolerance in the immune system, a crucial network of mechanisms that was discovered, discarded, and then rediscovered after a revolution in the tools we use to reveal and define immune phenomena. After this epic scientific journey, Davis completes the book with an account of how, for more than half a century, immunologists have striven to harness the power of the immune system against cancer. what better place to read about the dawn of success than in the final pages of this lucid and moving story.
Could you tell us a bit more about the potential to harness the immune system against cancer? It does not go unnoticed that biontech, which has developed one of the main vaccines against covid in association with pfizer, has had cancer in sight.
This is a very promising new area. The German biontech company was founded in 2008 specifically to develop immune-based cancer treatments. Cancer cells often have abnormal surface molecules that are not found on healthy cells, but for various reasons the immune system does not attack them. Biontech’s idea was to create vaccines containing these molecules, teaching the immune system to attack cells with abnormal markers. thus immunotherapeutic treatments were developed for melanoma and prostate cancer. Cancer markers are encoded in messenger RNA (mRNA) to ensure that the body mounts a strong immune response, as if dealing with invading germs.
When covid-19 emerged in early 2020, biontech quickly adapted its mrna technology to produce the spike protein of the coronavirus, exploiting its existing vaccine production system in what could be seen as the most successful business move in history. XXI century.
This strategy is complementary to the promising advances in cancer immunotherapy described in the final chapter of the beautiful cure. Earlier in his book, Davis details the ways in which the immune system exhibits restraint, inhibition, and tolerance to protect normal cells and processes in the body. in a chapter titled “future drugs,” he explains how these restrictions can be turned off very selectively in tumor patients, unleashing the power of the immune system against cancers like melanoma. the secret is to deactivate or “block” the off switches on the surface of the immune cells. Medications that do this are known as checkpoint inhibitor drugs and appear to work well in a proportion of patients. In the future, there may be scope to combine mRNA therapeutic cancer vaccines with checkpoint inhibitor drugs to maximize the efficacy of antitumor immunity.
your next immunology book choice is philip roth’s nemesis. this book had somehow escaped me and I thank you for highlighting it. tell us what you like about it.
philip roth sets what would be his last novel in the neighborhood of newark, new jersey, where he was born and raised. Before the 2020 pandemic, the race for a most famous vaccine took place in America in the middle of the century, funded entirely by voluntary donations from the American people: the race for a polio vaccine. nemesis describes a fictional outbreak of polio in 1944, eleven years before the vaccine. For me, the story has a great resonance with the events that unfolded in 2020. The fear of polio, initially untreatable like covid-19, was very great. Although facts and figures can convey the nature of a terrible pandemic or a terrible epidemic directed at children, emotional reality is best portrayed in works of fiction. the media has gone to great lengths to make the covid-19 experience, in intensive care units, for example, real to those not involved; but can we really get into the hearts and minds of those caught up in the contagion?
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“the story has a great resonance with the events that unfold in 2020. the use of masks becomes controversial. personal hygiene becomes obsessive”
roth is a complete success with its protagonist, bucky cantor, a young sports teacher whose identity and self-esteem are totally invested in his own physical prowess and his intense concern for the children in his care. Polio, the mysterious crippler and killer, threatens them both. I wish a vaccine could be found! suspicions about the source of infection haunt relations between communities. the use of masks becomes controversial. personal hygiene becomes obsessive. Roth escalates the tension by inflating the death rate. And then Bucky escapes to a kind of paradise: a summer camp in the mountains where his beloved waits for him and reveals the beauty of the natural world and her own perspectives. but he is doomed to be permanently paralyzed and there is no escape or remedy for the disease. In a final demonstration of his power as a writer, Roth ends the story with an indelible image of his young hero throwing the javelin at the pinnacle of his prowess.
When the polio vaccine arrived, no wonder it seemed like a miracle. a single vaccine to defeat the dreaded disease. the vaccine against covid-19 also miraculously arrived, first one, then two, three, four, five, missing half a dozen and a second generation. is a fitting testament to the science of immunology and the new technologies that make vaccines possible.
It seems that not everyone agrees. His latest book recommendation on the subject of immunology is Paul Offit’s Deadly Choices: How the Anti-Vaccine Movement Threatens Us All, published ten years ago. what does the book say and what, if anything, has changed?
Paul Offit is considered by many to be the leading authority on infectious diseases in children in the United States, and he wrote this important and insightful book in response to the growing problem of vaccine hesitancy in the late 20th and early 21st centuries. . century. Two major events were responsible for fueling what would turn out to be unfounded fears about vaccine safety. but once the damage was done, it proved very difficult to restore trust with large-scale consensus science. In 1974, a research article in the respected British medical journal described 36 children with epilepsy and linked their condition to pertussis (whooping cough) vaccination. this sowed the seeds of uncertainty. In Britain, uptake of the vaccine fell to 31 percent, while in Japan, just over 10 percent of children were vaccinated.
Another notorious publication, in 1998, did even more damage, when British scientists suggested that the MMR (measles, mumps, rubella) vaccine might be associated with autism. the paper was later discredited. offit meticulously traces the events surrounding these mishaps, how they breathed new life into the anti-vaccination movement, and how this resulted in hundreds of preventable cases of infectious disease in the 21st century. It also highlights the woeful failure to reap the benefits of new vaccines, such as the HPV vaccine introduced in 2006. Nearly 50 percent of children are left unprotected. Full acceptance of this vaccine would likely prevent about twenty-six thousand cases of cancer each year in the United States.
“in Great Britain, the acceptance of the vaccine fell to 31%, while in Japan, just over 10% of children were vaccinated”
but offit doesn’t stop there. In addition to documenting the decades-long, large-scale studies that strongly demonstrate the absence of a link between vaccines and developmental disorders, it details, in the case of seizures and arrested development, the real cause of the problem: a rare genetic problem. disorder discovered in 2006. Offit is widely admired for his wisdom and willingness to compromise and reassure those in doubt. While some authorities on vaccine hesitancy discuss the sociological reasons behind vaccine rejection, Offit is the leading proponent of objectivity, clinical investigation, and the paramount importance of scientific understanding.
since offit’s authorized publication in 2010, updated in 2015, the character of the anti-vaccination movement has changed and changed. During the 2020 pandemic, conspiracy theories related to the coronavirus, the content of covid-19 vaccines, and the motivation behind vaccination policy gained traction, leveraging the beliefs of right-wing libertarian extremists and proponents of leftist welfare philosophy. during the turbulent events surrounding the us. presidential campaign, radical anti-vaccinators sometimes found common cause with militant protest groups. however, the unprecedented success of the international collaborative effort to deliver safe and effective vaccines against covid-19 has strengthened the majority view that vaccination is a powerful global weapon and a force for good.
What are the frontiers of immunology today?
The pandemic highlights one of the unsolved problems in immunology. coronavirus is not a serious infection for most people. in most, the immune system easily prevails. But a large and growing group is highly vulnerable: the elderly. Before the 20th century, life expectancy was limited, but today most of us survive much longer. Understanding immunosenescence (how and why the immune system declines with age) is a major challenge for modern immunology.
another important frontier relates to youth. the increased incidence and severity of allergic diseases such as asthma remain to be explained and new therapies have been slow to emerge. overly aggressive immune responses may be related to modern hygiene and infection control. understanding this area will be important for future progress. the opposite problem, immunodeficiency disorders in the young, also remains a challenge.
As we saw in The Beautiful Cure, immune-mediated therapies for cancer have been elusive until recently. understanding how the immune system normally exerts restraint through regulatory cells has paved the way for new therapies. Blocking checkpoints that restrict immune responses has enormous potential to persuade immune cells to attack tumors. a complementary approach employs personalized cancer treatments. by identifying immune targets in tumors, it is possible to design individual cancer vaccines. This is precisely what biotech scientists were doing before covid-19: making personalized mRNA vaccines for people with melanoma and prostate cancer. they were also combining these vaccines with checkpoint inhibitor therapies. These strategies have great potential for the future.
despite the amazing success of covid-19 vaccines, we are still lacking highly effective vaccines against many diseases in the developing world. These include tuberculosis, malaria, hiv and diarrheal diseases, the leading causes of death for young children worldwide. Combination vaccines against diarrhea, designed to complement hygiene measures, are in the early stages of development.
Understanding the causes of autoimmune diseases and the rational development of more effective treatments is another important frontier. monoclonal antibodies for clinical use, designed to attack regulatory molecules of the immune system, have revolutionized the treatment of diseases such as rheumatoid arthritis, but there is still a long way to go. these specifically created antibodies have recently been bound to monoclonal t-cell receptors, engineered receptors that are extracted from cells and used as therapeutic drugs. Immunology has traditionally relied on curiosity-driven fundamental research to uncover secrets and enable the delivery of new therapies. But as you can see from these answers, 21st century research is very focused on multiple disease problems.
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